Pain is a major symptom in many medical conditions, and can significantly interfere with a person's quality of life and general functioning. Three categories of pain are generally recognized: nociceptive pain which is caused by stimulation of peripheral nerve fibers; inflammatory pain which is associated with tissue damage and the infiltration of immune cells; and pathological pain which is a disease state caused by damage to the nervous system or by its abnormal function (dysfunctional pain, like in fibromyalgia, irritable bowel syndrome, tension type headache, etc.). Acute pain is usually managed with medications such as analgesics and anesthetics.
A migraine headache is a chronic disorder characterized by moderate to severe headaches and nausea. It is believed to be a neurovascular disorder. Migraines typically present with recurrent severe headache associated with autonomic symptoms. The typical migraine headache is unilateral, throbbing, and moderate to severe, and can be aggravated by physical activity Initial treatment is with analgesics for the headache, an antiemetic for the nausea, and the avoidance of triggers. A number of analgesics are effective for treating migraines including: non-steroidal anti-inflammatory drugs (NSAIDs); paracetamol/acetaminophen; and simple analgesics combined with caffeine.
NSAIDs provide analgesic and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects. The term “nonsteroidal” distinguishes these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic. NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly prevalent. The two main adverse drug reactions associated with NSAIDs relate to gastrointestinal effects and renal effects of the agents.
NSAIDs can be classified based on their chemical structure or mechanism of action. Common NSAID classification groups include: Salicylates, Propionic acid derivatives, Acetic acid derivatives, Enolic acid derivatives, Fenamic acid derivatives, Selective COX-2 inhibitors, and Sulphonanilides. NSAIDs within a group tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds usually relate to dosing regimens, route of administration, and tolerability profile.
Ketoprofen is a nonsteroidal anti inflammatory proprionic acid derivative. It has potent anti inflammatory and analgesic activity. Conventionally, ketoprofen and other related drugs have been administered orally; however, they have been accompanied by systemic side effects or gastrointestinal irritation. In order to reduce these side effects, these drugs have been formulated as transdermal preparations. The skin permeability of these NSAIDs is known to be higher than other NSAIDs.
To minimize the foregoing drawbacks, attempts have been made to develop topical ketoprofen compositions. These attempts have been met with limited success due to photosensitivity and stability problems as well as photoallergy potential.